Polymyalgia rheumatica (PMR)
Conditions
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The following inclusion criteria need to be fulfilled in order to be eligible for the study: 1. Diagnosis of PMR as confirmed by the investigator at screening and at baseline, fulfilment (also in retrospect) of the provisional 2012 ACR-EULAR classification criteria (see table 1) [19,20] 2. Diagnosis of PMR of maximum 3 weeks established at screening visit. 3. GC naïve1 or on GC treatment for a maximum of 3 weeks at screening with an initial dose of maximum 25 mg/day. 4. Willing and able to receive oral prednisone 20 mg/day at randomization and to follow a pre-specified tapering regimen 5. Willing to receive treatment for prevention of GC-induced bone loss 6. Willing and being able to understand and follow the study procedures 7. Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential, means a. Women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation b. Women aged 55 years or older who are not on hormone therapy and who have had at least 6 months of spontaneous amenorrhea c. Women aged 55 years or older who have a diagnosis of menopause 8. Written informed consent 9. Female and Male subjects from = 50 years old and higher. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Evidence of GCA (cranial or large vessel) as indicated by unequivocal clinical symptoms (except PMR), imaging and/or biopsy results. Routine screening of eligible PMR patients for GCA with imaging methods or temporal artery biopsy is not recommended 2. Conditions other than PMR requiring continuous or intermittent treatment with oral or parenteral GCs or parenteral administration of GCs, unless the last exposure to GCs was >1 months before screening 3. Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis) 4. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening 5. Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient´s participation in the study. 6. Have experienced any of the following VTE (DVT/pulmonary embolism, myocardial infarction, unstable ischemic heart disease stroke, or New York Heart Association Stage III/IV heart failure within 12 weeks of screening. For Centres within Czech Republic patients with any history of it must not be included. 7. Have a history of recurrent (= 2) VTE (DVT/PE) 8. Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that in the opinion of the investigator could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data 9. Immunization with a live/attenuated vaccine within 12 weeks prior to baseline or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination at the discretion of the investigator) 10. Previous treatment with baricitinib, tofacitinib or tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis) 11. Have received plasmapheresis within 12 weeks of screening 12. Have screening laboratory test values, including thyroid-stimulating hormone (TSH), outside the reference range for the population that, in the opinion of the investigator, pose an unacceptable risk for the patient´s participation in the study. Patients who are receiving thyroxine as replacement therapy may participate in the study, provided stable therapy has been administered for = 12 weeks and TSH is within the laboratory´s range. Patients who have TSH marginally outside the laboratory´s normal reference range and are receiving stable thyroxine replacement therapy may participate if the treating physician has documented that the thyroxine replacement therapy is adequate for the patient 13. Have any of the following specific abnormalities on screening laboratory tests: a. ALT or AST >2 x ULN b. Alkaline phosphatase (ALP) =2 x ULN c. Total bilirubin = 1.5 x ULN d. Hemoglobin <9 g/dL (90.0 g/L) e. Total white blood cell count <2500 cells/µL (<2.50 x 103 / µL or <2.50 GI/L) f. Neutropenia (absolute neutrophil count [ANC] <1200 cells/ µL (<1.20 x 103/ µL or <1.20 GI/L) g. Lymphopenia (lymphocyte count <500 cells/µL) (<50 x 103/ µL or <50GI/L) h. Thrombocytopenia (platelets <100,000 cells/µL) (<100 x 103/µL or <100 GI/L) i. eGFR <60 mL/min/1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy and safety of baricitinib compared with placebo on top of rapidly tapered GC treatment in a double-blind, controlled study, with GC-free remission of disease as primary outcome. ;Secondary Objective: To assess the efficacy and safety of baricitinib compared with placebo on top of rapidly tapered GC treatment in a double-blind, controlled study, with GC-free remission of disease as primary outcome.;Primary end point(s): Proportion of subjects in GC-free remission at week 16 (Part I);Timepoint(s) of evaluation of this end point: See section E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects in GC free remission at week 12 (Part I), 28 (Part II) and 44 (Part III) • Cumulative prednisone doses at weeks 12, 16 (Part I), 28 (Part II) and 44 (Part III) • Number of relapses per patient at weeks 12, 16 (Part I), 28 (Part II) and 44 (Part III) • Time to first and second relapse • Glucocorticoid dose intensity (absolute and relative) at week 16 • Patient reported outcomes including SF-36, FACIT-Fatigue, HAQ, Patient Global Assessment of Disease Activity (PGA), Patient assessment of pain • Investigator reported outcomes including Evaluator Global Assessment of disease activity (EGA), duration and severity of Morning Stiffness, semiquantitative elevation of upper limbs’ scale • Laboratory markers of inflammation including ESR and CRP • Polymyalgia Rheumatica Activity Score (PMR-AS) • Occurrence of adverse events and serious adverse events, incidence of GC-related adverse events, changes in vital signs, haematology and clinical chemistry parameters ;Timepoint(s) of evaluation of this end point: See section E.5.2 | — |
Countries
Austria, Czech Republic, Italy
Contacts
Public ContactPrincipal Investigator
Daniel Aletaha
Outcome results
None listed